NIH Scientists Identify New Hirschsprung's Disease Gene

January 1998

BETHESDA, Md. - Researchers at the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) have identified another mutated gene that causes Hirschsprung's disease in laboratory mice.

The gene appears to be essential for proper development of part of the nervous system, they report in the January, 1998, issue of Nature Genetics. The scientists expect to find that the equivalent human gene, when mutated, also causes Hirschsprung's disease in people, as has been the case with the four previously discovered mouse Hirschsprung genes.

Hirschsprung's disease is a highly variable inborn disorder whose chief feature is impaired intestinal function in which part of the colon lacks nerve cells and so is unable to relax. The result is chronic constipation and distention of the abdomen. The disorder, which affects about one in 5,000 U.S. newborns, is usually diagnosed in infancy. Treatment involves surgical removal of the affected portion of the colon.

The scientists believe the product of the newly identified gene, which they call SOX10, is one of many transcription factors proteins that control which genes are expressed at any given time in any given tissue. The SOX10 protein appears in the very early embryo in the cells that will eventually become the peripheral nervous system (the nerves that conduct impulses to and from the spinal cord).

"By studying this gene and what genes it regulates we will really have an insight into the early development of the peripheral nervous system. So, in addition to its relevance for Hirschsprung's disease, this finding will provide a powerful tool to be used for future studies," said corresponding author William J. Pavan.

Dr. Pavan studies mouse development in NHGRI's Laboratory of Genetic Disease Research, where the research was done. NHGRI oversees the NIH's role in the Human Genome Project, an international research effort to develop tools for gene discovery.